Two overall objectives will be pursued in our continued efforts to treat patients with otherwise fatal[unreadable] nonmalignant hematologic diseases by allogeneic hematopoietic cell transplantation. One is to reduce[unreadable] regimen-related toxicities and transplant-related complications, including graft rejection and graft-vs-host[unreadable] disease. The other is to broaden the choice of hematopoietic cell donors beyond HLA-matched relatives and[unreadable] unrelated volunteers by including grafts of unrelated cord blood and HLA-haploidentical marrow cells.[unreadable] Nonmalignant disorders include three distinct disease entities, aplastic anemia. Fanconi anemia, and[unreadable] inherited diseases of the hematopoietic and immune systems.[unreadable] In order to assure accrual of patients with these relatively infrequent diseases to the proposed protocols,[unreadable] we have taken two steps. The first has been to include other academic centers as participants in the[unreadable] studies. The second, important for protocols involving patients with immunodeficiency diseases, has been to[unreadable] establish close collaborations with key members of the Pediatric Immunology group at the University of[unreadable] Washington/Children's Hospital and Regional Medical Center, who see and study many of these patients.[unreadable] The studies proposed under this Project have relevance for hematopoietic cell transplantation in patients[unreadable] with hemoglobinopathies, such as sickle cell disease and thalassemia major, autoimmune diseases, and[unreadable] those with malignant diseases, including myelodysplastic syndromes studied under Project 4 of this grant.[unreadable] Also, hematopoietic cell transplantation protocols, that are found to be both effective and safe for patients[unreadable] with hematologic diseases, might eventually be of interest in the treatment of recipients of solid organ grafts,[unreadable] e.g. kidney or lung. In that setting, a concurrent or preceding hematopoietic graft from the kidney or lung[unreadable] donor would provide an immunologic "platform" for the solid organ graft, which would be indefinitely[unreadable] accepted without the need for lifelong immunosuppression.